6LV0

Crystal structure of the soluble domain of the multiple peptide resistance factor (MprF) from Rhizobium tropici

Summary for 6LV0

• Entry DOI: 10.2210/pdb6lv0/pdb
• Descriptor: Low pH-inducible protein LpiA (2 entities in total)
• Functional Keywords: lipid biosynthesis, biosynthetic protein
• Biological source: Rhizobium tropici CIAT 899
• Total number of polymer chains: 2
• Total formula weight: 74261.07

Authors

Jiao, H.Z.,Song, D.F.,Liu, Z.F. (deposition date: 2020-02-02, release date: 2021-02-03, Last modification date: 2024-03-27)

Primary citation

Song, D.,Jiao, H.,Liu, Z.
Phospholipid translocation captured in a bifunctional membrane protein MprF.
Nat Commun, 12:2927-2927, 2021

PubMed Abstract: As a large family of membrane proteins crucial for bacterial physiology and virulence, the Multiple Peptide Resistance Factors (MprFs) utilize two separate domains to synthesize and translocate aminoacyl phospholipids to the outer leaflets of bacterial membranes. The function of MprFs enables Staphylococcus aureus and other pathogenic bacteria to acquire resistance to daptomycin and cationic antimicrobial peptides. Here we present cryo-electron microscopy structures of MprF homodimer from Rhizobium tropici (RtMprF) at two different states in complex with lysyl-phosphatidylglycerol (LysPG). RtMprF contains a membrane-embedded lipid-flippase domain with two deep cavities opening toward the inner and outer leaflets of the membrane respectively. Intriguingly, a hook-shaped LysPG molecule is trapped inside the inner cavity with its head group bent toward the outer cavity which hosts a second phospholipid-binding site. Moreover, RtMprF exhibits multiple conformational states with the synthase domain adopting distinct positions relative to the flippase domain. Our results provide a detailed framework for understanding the mechanisms of MprF-mediated modification and translocation of phospholipids.

PubMed: 34006869
DOI: 10.1038/s41467-021-23248-z

Experimental method

X-RAY DIFFRACTION (1.998 Å)